Anti-PD-L1 efficacy can be enhanced by inhibition of myeloid-derived suppressor cells with a selective inhibitor of PI3Kd/g

Cancer Research

Volumn 77, Issue 10, 2017, Pages 2607-2619

  Davis, Ruth J ^a   Moore, Ellen C ^a   Clavijo, Paul E ^a   Friedman, Jay ^a   Cash, Harrison ^a   Chen, Zhong ^a   Silvin, Chris ^a   Van Waes, Carter ^a   Allen, Clint ^a,b  

^a NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DUVELISIB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE DELTA; PHOSPHATIDYLINOSITOL 3 KINASE GAMMA; PROGRAMMED DEATH 1 LIGAND 1; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; EPITOPE; IPI-145; ISOQUINOLINE DERIVATIVE; MONOCLONAL ANTIBODY; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE 3 KINASE; PROTEIN KINASE INHIBITOR; PURINE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN SPECIFICITY; ARTICLE; CANCER SURVIVAL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; EFFECTOR CELL; ENZYME INHIBITION; EX VIVO STUDY; IMMUNOCOMPETENT CELL; IMMUNOSTIMULATION; IMMUNOSUPPRESSIVE TREATMENT; IN VIVO STUDY; MOUSE; MOUTH CANCER; MYELOID-DERIVED SUPPRESSOR CELL; NONHUMAN; PHARMACOLOGICAL BLOCKING; PRIMARY TUMOR; PRIORITY JOURNAL; PROTEIN EXPRESSION; TUMOR ASSOCIATED LEUKOCYTE; TUMOR GROWTH; TUMOR MICROENVIRONMENT; ANIMAL; ANTAGONISTS AND INHIBITORS; DISEASE MODEL; DRUG EFFECTS; IMMUNOLOGY; IMMUNOMODULATION; LYMPHOCYTE ACTIVATION; METABOLISM; NEOPLASMS; PATHOLOGY; SURVIVAL ANALYSIS; TUMOR CELL LINE;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, CD274; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CLASS I PHOSPHATIDYLINOSITOL 3-KINASES; DISEASE MODELS, ANIMAL; EPITOPES, T-LYMPHOCYTE; IMMUNOMODULATION; ISOQUINOLINES; LYMPHOCYTE ACTIVATION; LYMPHOCYTES, TUMOR-INFILTRATING; MICE; MYELOID-DERIVED SUPPRESSOR CELLS; NEOPLASMS; PROTEIN KINASE INHIBITORS; PURINES; SURVIVAL ANALYSIS; TUMOR MICROENVIRONMENT;

EID: 85020218220     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-16-2534     Document Type: Article

References (40)

1. Champiat S, Ferte C, Lebel-Binay S, Eggermont A, Soria JC. Exomics and immunogenics: Bridging mutational load and immune checkpoints efficacy. Oncoimmunology 2014;3:e27817.
2. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancerassociated genes. Nature 2013;499:214-8.
3. The Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015; 517:576-82.
4. Keck MK, Zuo Z, Khattri A, Stricker TP, Brown CD, Imanguli M, et al. Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res 2015;21: 870-81.
5. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 2013;14:1014-22.
6. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Translat Med 2012;4:127ra37.
7. Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE- 012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17: 956-65.
8. Gabrilovich DI,Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9:162-74.
9. Vasquez-Dunddel D, Pan F, Zeng Q, Gorbounov M, Albesiano E, Fu J, et al. STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients. J Clin Invest 2013;123:1580-9.
10. Davis RJ, Van Waes C, Allen CT. Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer. Oral Oncol 2016;58:59-70.
11. Young MR, Petruzzelli GJ, Kolesiak K, Achille N, Lathers DM, Gabrilovich DI. Human squamous cell carcinomas of the head and neck chemoattract immune suppressive CD34(+) progenitor cells. Human Immunol 2001; 62:332-41.
12. Gabrilovich DI, Bronte V, Chen SH, Colombo MP, Ochoa A, Ostrand- Rosenberg S, et al. The terminology issue for myeloid-derived suppressor cells. Cancer Res 2007;67:425; author reply 26.
13. Arina A, Schreiber K, Binder DC, Karrison TG, Liu RB, Schreiber H. Adoptively transferred immune T cells eradicate established tumors despite cancer-induced immune suppression. J Immunol 2014;192: 1286-93.
14. Pak AS, Wright MA, Matthews JP, Collins SL, Petruzzelli GJ, Young MR. Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin Cancer Res 1995;1:95-103.
15. Weed DT, Vella JL, Reis IM, De la Fuente AC, Gomez C, Sargi Z, et al. Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res 2015;21: 39-48.
16. Gabitass RF, Annels NE, Stocken DD, Pandha HA, Middleton GW. Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother 2011;60:1419-30.
17. Loukinova E, Dong G, Enamorado-Ayalya I, Thomas GR, Chen Z, Schreiber H, et al. Growth regulated oncogene-alpha expression by murine squamous cell carcinoma promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a host CXC receptor-2 dependent mechanism. Oncogene 2000;19:3477-86.
18. Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol 2010;11:329-41.
19. Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ, Gorjestani S, et al. PI3Kgamma is a molecular switch that controls immune suppression. Nature 2016;539:437-42.
20. De Henau O, Rausch M, Winkler D, Campesato LF, Liu C, Cymerman DH, et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kgamma in myeloid cells. Nature 2016;539:443-47.
21. Ali K, Soond DR, Pineiro R, Hagemann T, Pearce W, Lim EL, et al. Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature 2014;510:407-11.
22. Winkler DG, Faia KL, DiNitto JP, Ali JA, White KF, Brophy EE, et al. PI3Kdelta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol 2013;20:1364-74.
23. Ian Flinn YO, Patel M, Horwitz SM, Foss FM, Sweeney J, Allen K, et al. a Phase 1 evaluation of duvelisib (IPI-145), a PI3K-δ,γ inhibitor, in patients with relapsed/refractory iNHL. Blood 2014;124:802.
24. Moore EC, Cash HA, Caruso AM, Uppaluri R, Hodge JW, Van Waes C, et al. Enhanced tumor control with combination mTOR and PD-L1 inhibition in syngeneic oral cavity cancers. Cancer Immunol Res 2016; 4:611-20.
25. Judd NP, Winkler AE, Murillo-Sauca O, Brotman JJ, Law JH, Lewis JS Jr, et al. ERK1/2 regulation of CD44 modulates oral cancer aggressiveness. Cancer Res 2012;72:365-74.
26. Davis RJ, Silvin C, Allen CT. Avoiding phagocytosis-related artifact in myeloid derived suppressor cell T-lymphocyte suppression assays. J Immunol Methods 2016: S0022-1759.
27. Roederer M.Interpretation of cellular proliferation data: avoid the panglossian. Cytometry A 2011;79:95-101.
28. Moore E, Clavijo PE, Davis R, Cash H, Van Waes C, Kim Y, et al. Established T cell-inflamed tumors rejected after adaptive resistance was reversed by combination STING Activation and PD-1 pathway blockade. Cancer Immunol Res 2016;4:1061-1071.
29. Ji RR, Chasalow SD, Wang L, Hamid O, Schmidt H, Cogswell J, et al. An immune-active tumor microenvironment favors clinical response to ipilimumab. Cancer Immunol Immunother 2012;61:1019-31.
30. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014;371:2189-99.
31. Sahin E, Haubenwallner S, Kuttke M, Kollmann I, Halfmann A, Dohnal AM, et al. Macrophage PTEN regulates expression and secretion of arginase I modulating innate and adaptive immune responses. J Immunol 2014; 193:1717-27.
32. Choi WS, Seo YB, Shin PG, Kim WY, Lee SY, Choi YJ, et al. Veratric acid inhibits iNOS expression through the regulation of PI3K activation and histone acetylation in LPS-stimulated RAW264.7 cells. Int J Mol Med 2015;35:202-10.
33. Pauleau AL, Rutschman R, Lang R, Pernis A, Watowich SS, Murray PJ. Enhancer-mediated control of macrophage-specific arginase I expression. J Immunol 2004;172:7565-73.
34. Dickensheets H, Vazquez N, Sheikh F, Gingras S, Murray PJ, Ryan JJ, et al. Suppressor of cytokine signaling-1 is an IL-4-inducible gene in macrophages and feedback inhibits IL-4 signaling. Genes Immun 2007;8:21-7.
35. Kaneda MM, Cappello P, Nguyen AV, Ralainirina N, Hardamon CR, Foubert P, et al. Macrophage PI3Kgamma drives pancreatic ductal adenocarcinoma progression. Cancer Discov 2016;6:870-85.
36. Soond DR, Bjorgo E, Moltu K, Dale VQ, Patton DT, Torgersen KM, et al. PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans. Blood 2010;115: 2203-13.
37. Younis RH, Han KL, Webb TJ. Human head and neck squamous cell carcinoma-associated semaphorin 4D induces expansion of myeloidderived suppressor cells. J Immunol 2016;196:1419-29.
38. Strauss L, Bergmann C, Szczepanski M, Gooding W, Johnson JT, Whiteside TL. A unique subset of CD4+CD25highFoxp3+ T cells secreting interleukin- 10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin Cancer Res 2007;13:4345-54.
39. Whiteside TL.Induced regulatory T cells in inhibitory microenvironments created by cancer. Expert Opin Biol Ther 2014;14:1411-25.
40. Liu C, Workman CJ, Vignali DA. Targeting regulatory T cells in tumors. FEBS J 2016;283:2731-48.